Contact Lens & Anterior Eye 38 (2015) 59–60
Contents lists available at ScienceDirect
Contact Lens & Anterior Eye journal homepage: www.elsevier.com/locate/clae
Case report
Ocular side effects and trichomegaly of eyelashes induced by erlotinib: A case report and review of the literature Tuba Celik a,∗ , Mustafa Kosker b a b
Department of Ophthalmology, Bolu Gerede State Hospital, Seviller Street, 14900 Gerede-Bolu, Turkey Department of Ophthalmology, Ulus State Hospital, Turkey
a r t i c l e
i n f o
Article history: Received 2 February 2014 Received in revised form 19 August 2014 Accepted 28 August 2014 Keywords: Erlotinib Trichomegaly Eyelashes
a b s t r a c t Therapeutics belonging to the group of epidermal growth factor inhibitors are currently in widespread use for the treatment of certain malignancies, especially in advanced non-small cell lung cancer. A wide spectrum of the cutaneous side effects of these drugs are well known but the ocular side effects and trichomegaly of eyelashes are rarely reported, particularly for an ophthalmology audience. This report presents a case of erlotinib induced eyelash trichomegaly and the other ocular side effects of this drug in a 74 year-old female patient with metastatic lung adenocarcinoma. Trichomegaly is not a drug-limiting side effect, however long eyelashes often cause eyeball irritation and corneal epithelial defects. Herein, the authors emphasize the importance of recognizing this side effect in order to avoid from severe complications such as corneal ulcers in uncared patients. © 2014 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.
1. Introduction
2. Case report
Epidermal growth factor receptor inhibitors are the major component of molecular focused therapies in fighting advanced cancers [1,2]. The tyrosine kinase inhibitors (TKIs) target the epidermal growth factor receptor (EGFR) tyrosine kinase (TK), which is expressed on cell surface [1]. Erlotinib and gefitinib are the most well known EGFR TKIs act by blocking intracellular phosphorylation of EGFR [2]. These drugs bind reversibly to the adenosine triphosphate binding zone of EGFR. Therefore, inhibition of ATP results in blockage of the signal cascades [3,4]. EGFR is also located in hair follicle, keratinocytes and sweat glands. Therefore, clinicians were frequently encountered with various cutaneous effects of EGFR TKIs such as acneiform skin rash, pruritus, xerosis, skin fissures, telangiectasias, paronychia and hair changes [1]. Trichomegaly of the eyelashes is an uncommon untoward effect of EGFR inhibitor therapy which is characterized by excessive overgrowth of eyelashes [5]. This report presents a case of erlotinib induced eyelash trichomegaly and the other ocular side effects of this drug in a female patient who received erlotinib for lung adenocarcinoma.
A 74 year-old female patient with no history of smoking was admitted to our clinic with complaints of ocular irritation and excessive elongation of both eyelashes. She had been diagnosed with stage 4 lung adenocarcinoma for which she had received four cycles of chemotherapy with cisplatin and irinotecan. While the disease was shown to be stabilized in initial months after the chemotherapy, new pulmonary nodules and new metastases of bones developed in following months. Subsequently the treatment was switched to systemic epidermal growth factor receptor inhibition with the tyrosine kinase inhibitor, erlotinib (Tarceva® , Roche), 150 mg per day orally. During the treatment, she has experienced skin rash on her face and irregular growth of the eyelashes that irritated the eyeballs (Fig. 1). Examination revealed blepharitis and tear film dysfunction. No corneal disorder was noticed meanwhile examining the anterior segment. The patient has received erlotinib monotherapy for six months and her lung cancer was shown to be responsed to the treatment partially. Thus, the therapy is still continuing and she handles elongation of the eyelashes by trimming with scissors monthly. Intensive topical lubrication was also initiated as supplementary treatment and her ocular irritation has greatly improved.
3. Discussion ∗ Corresponding author. Tel.: +90 533 544 12 54; fax: +90 374 325 23 42. E-mail addresses: [email protected] (T. Celik), [email protected] (M. Kosker).
Eyelash trichomegaly is an uncommon drug-associated finding experienced during the treatment with certain drugs such
http://dx.doi.org/10.1016/j.clae.2014.08.005 1367-0484/© 2014 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.
60
T. Celik, M. Kosker / Contact Lens & Anterior Eye 38 (2015) 59–60
Fig. 1. Skin rash and trichomegaly of eyelashes induced by erlotinib treatment.
as latanoprost, bimatoprost, cyclosporine, zidovudine, tacrolimus, minoxidil, interferon-alpha, topiramate and EGFR inhibitors [1,5]. EGFR is presented in the eye at the level of corneal and conjunctival epithelial cells. It is also located in the outer root sheath of the hair follicle and plays an important role in hair cycle [6]. In addition to the antitumor activity, EGFR inhibitors such as erlotinib and gefitinib may block EGFR signaling and induce abnormal hair growth [2]. The incidence of trichomegaly induced by erlotinib has not been accurately assessed. Despite the widespread use of this drug in metastatic non-small cell cancer, there have been a few cases reported until today, particularly for an ophthalmology audience [7–10]. This case had also been diagnosed with metastatic lung adenocarcinoma for which she has used erlotinib as a second line chemotherapy for 6 months. In addition to exuberant growth of eyelashes, she has also demonstrated dysfunctional tear syndrome and blepharitis as other ocular side effects of erlotinib. Trichomegaly is not a drug-limiting side effect, however long eyelashes often cause eyeball irritation and corneal epithelial defects. Corneal ulcers may rarely be seen in the more severe cases. Only two reports in the literature demonstrate corneal ulcers resulting from trichomegaly induced by erlotinib therapy. Firstly Lane and Goldenstein [11] two years later Jazeyari and Malhotra [12] reported their cases which were complicated with corneal ulcers. Both of the cases had benefited from epilation and lid hygiene and they had remained symptom free with topical lubrication. The authors have not encountered with corneal ulcer in the patient and she has been successfully treated with eyelash trimming and topical lubrication. More recently, uveitis has been reported as a new ocular side effect of erlotinib therapy [13,14]. Ali et al. [14] reported a case of erlotinib induced bilateral anterior uveitis in a 68 year-old female patient with lung adenocarcinoma. They had stopped erlotinib therapy after the occurring of ocular symptoms of uveitis. The patient reported improved well being and no further symptoms of uveitis were noted up to 6 month follow-up. Corneal ulcers and uveitis are uncommon but potentially sight threatening complications of erlotinib therapy that have been reported until today [11–14]. The wider use of this treatment might cause increased risk of these complications but it is not clearly known whether these complications are needed drug limiting or not. Thus, clinicians should be aware of these uncommon ocular side effects in using erlotinib monotherapy. Occurrence of acneiform skin rash is known to be associated with better tumor responses to erlotinib. Although many clinical studies have supported that patients with cutaneous reactions have better survival than those with no cutaneous manifestations, the clinical significance of trichomegaly is currently unknown [15].
So far, all published studies on this subject and also our subject provided that positive tumor responses were observed in patients developing trichomegaly [3,4,10]. Unfortunately these reports are inadequate in numbers and prospective studies in large case series are needed to verify whether trichomegaly can have predictive role or not in the treatment. Ethical approval Written informed consent was obtained from the patient. Conflict of interest No author has a financial or proprietary interest in any material or method mentioned. References [1] Fox LP. Pathology and management of dermatologic toxicities associated with anti-EGFR therapy. Oncology (Wiiliston Park) 2006;20:26–34. [2] Pascual JC, Banuls J, Belinchon I, Blanes M, Massuti B. Trichomegaly following treatment with gefitinib (ZD1839). Br J Dermatol 2004;151:1111–2. [3] Munoz J, Hanbali AS. Epidermal growth factor receptor-induced hirsutism and trichomegaly. Mayo Clin Proc 2011;86(11):e50. [4] Jeon SH, Ryu JS, Choi GS, Kim JS, Kwon HY, Kim MS, et al. Erlotinib induced trichomegaly of the eyelashes. Tuberc Respir Dis (Seoul) 2013;74(1): 37–40. [5] Fabbrocini G, Panariello L, Cacciapuoti S, Bianca D, Ayala F. Trichomegaly of the eyelashes during therapy with epidermal growth factor receptor inhibitors: report of 3 cases. Dermatitis 2012;23(5):237–8. [6] Borkar DS, Lacouture ME, Basti S. Spectrum of ocular toxicities from epidermal growth factor receptor inhibitors and their intermediate-term follow-up: a five-year review. Support Care Cancer 2013;21(4):1167–74. [7] Zhang G, Basti S, Jampol LM. Acquired trichomegaly and symptomatic external ocular changes in patients receiving epidermal growth factor receptor inhibitors: case reports and a review of literature. Cornea 2007;26:858–60. [8] Papadopoulos R, Chasapi V, Bachariou A. Trichomegaly induced by erlotinib. Orbit 2008;27(4):329–30. [9] Desai RU, Rachakonda LP, Saffra NA. Trichomegaly secondary to erlotinib. Can J Ophthalmol 2009;44(6):e65. [10] Saif MW, Gnanaraj J. Erlotinib-induced trichomegaly in a male patient with pancreatic cancer. Cutan Ocul Toxicol 2010;29(1):62–6. [11] Lane K, Goldenstein SM. Erlotinib-associated trichomegaly. Ophthalmic Plast Surg 2007;23:65–6. [12] Jazayeri F, Malhotra R. A case of acquired trichomegaly following treatment with erlotinib. BMJ Case Rep 2009, http://dx.doi.org/10.1136/bcr.01.2009.1473, pii:bcr01.2009.1473. [13] Lim LT, Blum RA, Cheng CP, Hanifudin A. Bilateral anterior uveitis secondary to erlotinib. Eur J Clin Pharmacol 2010;66(12):1277–8. [14] Ali K, Kumar I, Usman-Saeed M, Usman Saeed M. Erlotinibrelated bilateral anterior uveitis. BMJ Case Rep 2011, http://dx.doi.org/10.1136/bcr.03.2011.3988, pii:bcr03.2011.3988. [15] Pérez-Soler R, Chachoua A, Hammond LA, Rowinsky EK, Huberman M, Karp D, et al. Determinants of tumor response and survival with erlotinib in patients with non—small-cell lung cancer. J Clin Oncol 2004;22(16):3238–47.
Contents lists available at ScienceDirect
Contact Lens & Anterior Eye journal homepage: www.elsevier.com/locate/clae
Case report
Ocular side effects and trichomegaly of eyelashes induced by erlotinib: A case report and review of the literature Tuba Celik a,∗ , Mustafa Kosker b a b
Department of Ophthalmology, Bolu Gerede State Hospital, Seviller Street, 14900 Gerede-Bolu, Turkey Department of Ophthalmology, Ulus State Hospital, Turkey
a r t i c l e
i n f o
Article history: Received 2 February 2014 Received in revised form 19 August 2014 Accepted 28 August 2014 Keywords: Erlotinib Trichomegaly Eyelashes
a b s t r a c t Therapeutics belonging to the group of epidermal growth factor inhibitors are currently in widespread use for the treatment of certain malignancies, especially in advanced non-small cell lung cancer. A wide spectrum of the cutaneous side effects of these drugs are well known but the ocular side effects and trichomegaly of eyelashes are rarely reported, particularly for an ophthalmology audience. This report presents a case of erlotinib induced eyelash trichomegaly and the other ocular side effects of this drug in a 74 year-old female patient with metastatic lung adenocarcinoma. Trichomegaly is not a drug-limiting side effect, however long eyelashes often cause eyeball irritation and corneal epithelial defects. Herein, the authors emphasize the importance of recognizing this side effect in order to avoid from severe complications such as corneal ulcers in uncared patients. © 2014 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.
1. Introduction
2. Case report
Epidermal growth factor receptor inhibitors are the major component of molecular focused therapies in fighting advanced cancers [1,2]. The tyrosine kinase inhibitors (TKIs) target the epidermal growth factor receptor (EGFR) tyrosine kinase (TK), which is expressed on cell surface [1]. Erlotinib and gefitinib are the most well known EGFR TKIs act by blocking intracellular phosphorylation of EGFR [2]. These drugs bind reversibly to the adenosine triphosphate binding zone of EGFR. Therefore, inhibition of ATP results in blockage of the signal cascades [3,4]. EGFR is also located in hair follicle, keratinocytes and sweat glands. Therefore, clinicians were frequently encountered with various cutaneous effects of EGFR TKIs such as acneiform skin rash, pruritus, xerosis, skin fissures, telangiectasias, paronychia and hair changes [1]. Trichomegaly of the eyelashes is an uncommon untoward effect of EGFR inhibitor therapy which is characterized by excessive overgrowth of eyelashes [5]. This report presents a case of erlotinib induced eyelash trichomegaly and the other ocular side effects of this drug in a female patient who received erlotinib for lung adenocarcinoma.
A 74 year-old female patient with no history of smoking was admitted to our clinic with complaints of ocular irritation and excessive elongation of both eyelashes. She had been diagnosed with stage 4 lung adenocarcinoma for which she had received four cycles of chemotherapy with cisplatin and irinotecan. While the disease was shown to be stabilized in initial months after the chemotherapy, new pulmonary nodules and new metastases of bones developed in following months. Subsequently the treatment was switched to systemic epidermal growth factor receptor inhibition with the tyrosine kinase inhibitor, erlotinib (Tarceva® , Roche), 150 mg per day orally. During the treatment, she has experienced skin rash on her face and irregular growth of the eyelashes that irritated the eyeballs (Fig. 1). Examination revealed blepharitis and tear film dysfunction. No corneal disorder was noticed meanwhile examining the anterior segment. The patient has received erlotinib monotherapy for six months and her lung cancer was shown to be responsed to the treatment partially. Thus, the therapy is still continuing and she handles elongation of the eyelashes by trimming with scissors monthly. Intensive topical lubrication was also initiated as supplementary treatment and her ocular irritation has greatly improved.
3. Discussion ∗ Corresponding author. Tel.: +90 533 544 12 54; fax: +90 374 325 23 42. E-mail addresses: [email protected] (T. Celik), [email protected] (M. Kosker).
Eyelash trichomegaly is an uncommon drug-associated finding experienced during the treatment with certain drugs such
http://dx.doi.org/10.1016/j.clae.2014.08.005 1367-0484/© 2014 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.
60
T. Celik, M. Kosker / Contact Lens & Anterior Eye 38 (2015) 59–60
Fig. 1. Skin rash and trichomegaly of eyelashes induced by erlotinib treatment.
as latanoprost, bimatoprost, cyclosporine, zidovudine, tacrolimus, minoxidil, interferon-alpha, topiramate and EGFR inhibitors [1,5]. EGFR is presented in the eye at the level of corneal and conjunctival epithelial cells. It is also located in the outer root sheath of the hair follicle and plays an important role in hair cycle [6]. In addition to the antitumor activity, EGFR inhibitors such as erlotinib and gefitinib may block EGFR signaling and induce abnormal hair growth [2]. The incidence of trichomegaly induced by erlotinib has not been accurately assessed. Despite the widespread use of this drug in metastatic non-small cell cancer, there have been a few cases reported until today, particularly for an ophthalmology audience [7–10]. This case had also been diagnosed with metastatic lung adenocarcinoma for which she has used erlotinib as a second line chemotherapy for 6 months. In addition to exuberant growth of eyelashes, she has also demonstrated dysfunctional tear syndrome and blepharitis as other ocular side effects of erlotinib. Trichomegaly is not a drug-limiting side effect, however long eyelashes often cause eyeball irritation and corneal epithelial defects. Corneal ulcers may rarely be seen in the more severe cases. Only two reports in the literature demonstrate corneal ulcers resulting from trichomegaly induced by erlotinib therapy. Firstly Lane and Goldenstein [11] two years later Jazeyari and Malhotra [12] reported their cases which were complicated with corneal ulcers. Both of the cases had benefited from epilation and lid hygiene and they had remained symptom free with topical lubrication. The authors have not encountered with corneal ulcer in the patient and she has been successfully treated with eyelash trimming and topical lubrication. More recently, uveitis has been reported as a new ocular side effect of erlotinib therapy [13,14]. Ali et al. [14] reported a case of erlotinib induced bilateral anterior uveitis in a 68 year-old female patient with lung adenocarcinoma. They had stopped erlotinib therapy after the occurring of ocular symptoms of uveitis. The patient reported improved well being and no further symptoms of uveitis were noted up to 6 month follow-up. Corneal ulcers and uveitis are uncommon but potentially sight threatening complications of erlotinib therapy that have been reported until today [11–14]. The wider use of this treatment might cause increased risk of these complications but it is not clearly known whether these complications are needed drug limiting or not. Thus, clinicians should be aware of these uncommon ocular side effects in using erlotinib monotherapy. Occurrence of acneiform skin rash is known to be associated with better tumor responses to erlotinib. Although many clinical studies have supported that patients with cutaneous reactions have better survival than those with no cutaneous manifestations, the clinical significance of trichomegaly is currently unknown [15].
So far, all published studies on this subject and also our subject provided that positive tumor responses were observed in patients developing trichomegaly [3,4,10]. Unfortunately these reports are inadequate in numbers and prospective studies in large case series are needed to verify whether trichomegaly can have predictive role or not in the treatment. Ethical approval Written informed consent was obtained from the patient. Conflict of interest No author has a financial or proprietary interest in any material or method mentioned. References [1] Fox LP. Pathology and management of dermatologic toxicities associated with anti-EGFR therapy. Oncology (Wiiliston Park) 2006;20:26–34. [2] Pascual JC, Banuls J, Belinchon I, Blanes M, Massuti B. Trichomegaly following treatment with gefitinib (ZD1839). Br J Dermatol 2004;151:1111–2. [3] Munoz J, Hanbali AS. Epidermal growth factor receptor-induced hirsutism and trichomegaly. Mayo Clin Proc 2011;86(11):e50. [4] Jeon SH, Ryu JS, Choi GS, Kim JS, Kwon HY, Kim MS, et al. Erlotinib induced trichomegaly of the eyelashes. Tuberc Respir Dis (Seoul) 2013;74(1): 37–40. [5] Fabbrocini G, Panariello L, Cacciapuoti S, Bianca D, Ayala F. Trichomegaly of the eyelashes during therapy with epidermal growth factor receptor inhibitors: report of 3 cases. Dermatitis 2012;23(5):237–8. [6] Borkar DS, Lacouture ME, Basti S. Spectrum of ocular toxicities from epidermal growth factor receptor inhibitors and their intermediate-term follow-up: a five-year review. Support Care Cancer 2013;21(4):1167–74. [7] Zhang G, Basti S, Jampol LM. Acquired trichomegaly and symptomatic external ocular changes in patients receiving epidermal growth factor receptor inhibitors: case reports and a review of literature. Cornea 2007;26:858–60. [8] Papadopoulos R, Chasapi V, Bachariou A. Trichomegaly induced by erlotinib. Orbit 2008;27(4):329–30. [9] Desai RU, Rachakonda LP, Saffra NA. Trichomegaly secondary to erlotinib. Can J Ophthalmol 2009;44(6):e65. [10] Saif MW, Gnanaraj J. Erlotinib-induced trichomegaly in a male patient with pancreatic cancer. Cutan Ocul Toxicol 2010;29(1):62–6. [11] Lane K, Goldenstein SM. Erlotinib-associated trichomegaly. Ophthalmic Plast Surg 2007;23:65–6. [12] Jazayeri F, Malhotra R. A case of acquired trichomegaly following treatment with erlotinib. BMJ Case Rep 2009, http://dx.doi.org/10.1136/bcr.01.2009.1473, pii:bcr01.2009.1473. [13] Lim LT, Blum RA, Cheng CP, Hanifudin A. Bilateral anterior uveitis secondary to erlotinib. Eur J Clin Pharmacol 2010;66(12):1277–8. [14] Ali K, Kumar I, Usman-Saeed M, Usman Saeed M. Erlotinibrelated bilateral anterior uveitis. BMJ Case Rep 2011, http://dx.doi.org/10.1136/bcr.03.2011.3988, pii:bcr03.2011.3988. [15] Pérez-Soler R, Chachoua A, Hammond LA, Rowinsky EK, Huberman M, Karp D, et al. Determinants of tumor response and survival with erlotinib in patients with non—small-cell lung cancer. J Clin Oncol 2004;22(16):3238–47.
